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Biomedical subjects

T Suda

Publications and source records attributed to T Suda.

At least 217 records · Page 12Linked to original sources
PubMed1999

[Pyothorax associated lymphoma treated by chemotherapy after thoracostomy].

A 62-year-old man with a medical history that included artificial pneumothorax therapy at the age of 18 was admitted to our hospital because of persistent cough. Chest computed tomographic scans disclosed atelectasis in the right lung and pyothorax surrounded by calcifications. Radiographic examination failed to disclose any tumors. After admission, high grade fever developed due to aggravated pyothorax infection. Because antibiotic therapy and drainage failed, open window thoracostomy was performed. Tumors were found along the wall of the pyothorax cavity, and examination of resected specimens yielded a diagnosis of non-Hodgkin's lymphoma, diffuse large cell type (B-cell lineage). It was difficult to close the pyothorax cavity due to infection and lymphoma. Therefore, with the thoracic window open, the patient was given combination chemotherapy including CHOP (6 courses) and DeVIC (7 courses). He died of disseminated intravascular coagulation 17 months after thoracostomy. In patients with pyothorax associated lymphoma, chemotherapy is sometimes difficult to perform because of persistent pyothorax infection. Although edema and ascites due to protein loss from the tumor complicated the treatment of our patient, we concluded that open window thoracostomy is effective in managing pyothorax prior to and during chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Sequential changes in hormone levels in postmenopausal breast cancer patients under long-term treatment with an aromatase inhibitor. Kanagawa AI Study Group].

Sequential changes in hormone levels were assessed for one year in postmenopausal breast cancer patients administered the aromatase inhibitor fodrozole hydrochloride hydrate (Afema) in order to evaluate its efficacy and safety in long-term treatment. Forty patients received Afema alone as postoperative adjuvant therapy, while 30 received it with 5-FU. Plasma estrone and estradiol levels decreased significantly in both groups (p < 0.001) and were not affected by body mass index (BMI). Plasma androstenedione and testosterone levels increased within the normal range. Aldosterone levels hit bottom 3 months after treatment was started, and tended to return to the pre-treatment baseline thereafter. Plasma cortisol levels increased significantly within the normal range. FDP and alpha 2-PIPC, parameters related to blood coagulation and fibrinolysis, showed no significant change. Adverse reactions, mainly nausea and elevation of LDH levels, were all slight. Thus, long-term administration of Afema resulted in significant decreases in estrogen levels with few adverse reactions regardless of the BMI, suggesting that it can be safely used as effective postoperative adjuvant therapy.

Aged↗
PubMed1999

[Functional evaluation of the hypothalamic-pituitary-adrenal axis].

The regulation of hypothalamic pituitary-adrenal (HPA) axis is controlled by three major factors: stress, circadian rhythm and negative feedback. Hypothalamic CRF binds to CRF receptor on ACTH cells and stimulates synthesis and secretion of ACTH. However, vasopressin binds to V1b receptor and enhances CRF induced ACTH secretion. ACTH stimulate secretion of cortisol and DHEA-S. Cortisol inhibits secretion of CRF and ACTH with negative feedback mechanism. To evaluate the ability of the hypothalamus to secrete CRF, insulin-induced hypoglycemia and metyrapone tests are used. For evaluation of the secretion of pituitary ACTH and adrenal cortisol, a CRF test is useful. Autonomic secretion of ACTH and/or cortisol is evaluated with a dexamethasone suppression test.

Adrenocorticotropic Hormone↗
PubMed1999

Pharmacokinetics of bisoprolol and its effect on dialysis refractory hypertension.

The efficacy, safety, and pharmacokinetics of bisoprolol were investigated following oral administration once daily for 12 weeks in hyperreninemic patients with dialysis-refractory hypertension. Mean blood pressure rapidly fell from 132 to 112 mmHg in the 5.0-mg/day (n = 6) and from 142 to 128 mmHg in the 2.5-mg/day patients (n = 5), which were accompanied by a fall in plasma renin activity. On nondialysis days, Cmax and T1/2 were significantly higher in patients than in healthy control subjects. However, Cmax in the 2.5-mg/day patients was almost equal to that in healthy control subjects receiving 5.0 mg/day of bisoprolol. Plasma bisoprolol was dialyzable. During the course of the study, dialysis hypotension and bradycardia occurred in two patients receiving 5.0 mg/day of bisoprolol. In conclusion, a daily dose of 2.5 mg bisoprolol seems to be an adequate and relatively effective dose in our patients with dialysis-refractory hypertension.

Administration, Oral↗
PubMed1998

Expression and functional analysis of a hemopoietic progenitor antigen, NJ-1 (114/A10), in the megakaryocytic lineage.

To analyze the functions of molecules expressed in hemopoietic progenitor cells, we obtained several monoclonal antibodies by immunizing Wistar rats with antigens from a murine immature leukemic cell line, DA-1. Here, we characterize one antibody designated NJ-1, which recognizes a 145-kd molecule, and identify the cDNA encoding the NJ-1 antigen by retrovirus-mediated expression cloning. Sequence analysis of the cDNA reveals that it is identical to a previously reported cDNA encoding a surface molecule of 573 amino acids recognized by monoclonal antibody 114/A10. Our studies show that expression of NJ-1 antigen is upregulated in a murine megakaryoblastic cell line, L8057, when it differentiates into a megakaryocytic lineage in response to 12-O-tetradecanoyl phorbol-13-acetate. Overexpression of NJ-1 antigen in L8057 cells inhibits cell adhesion to fibronectin, suggesting that it may act as a negative regulator of cell adhesion in the megakaryocytic lineage.

Animals↗
PubMed1998

Potential role of cbfa1, an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis: regulation of mRNA expression of osteoclast differentiation factor (ODF).

The role of Cbfa1 (core binding factor alpha1), an essential transcriptional factor for osteoblast differentiation, in osteoclastogenesis was investigated in vitro and in vivo using Cbfa1-deficient calvarial cells and mice. Co-cultures of calvarial cells isolated from embryos with three different Cbfa1 genotypes (Cbfa1+/+, Cbfa1+/- and Cbfa1-/-) and normal spleen cells generated TRAP-positive multinucleated osteoclast-like cells (OCLs) in response to 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] and dexamethasone, but the number and bone-resorbing activity of OCLs formed in co-culture with Cbfa1-/- calvarial cells were significantly decreased in comparison with those formed in co-cultures with Cbfa1+/+ or Cbfa1+/- calvarial cells. The expression of osteoclast differentiation factor/osteoprotegerin ligand (ODF/OPGL) mRNA was increased by the treatment with 1alpha, 25(OH)2D3 and dexamethasone in calvarial cells from Cbfa1+/+ and Cbfa1+/- mouse embryos, but not from Cbfa1-/- embryos. In contrast, the expression of osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF) mRNA was inhibited by 1alpha,25(OH)2D3 and dexamethasone similarly in all three types of calvarial cells. ODF/OPGL and OPG/OCIF mRNAs were highly expressed in the tibia and femur of Cbfa1+/+ and Cbfa1+/- embryos. In the tibia and femur of Cbfa1-/- embryos, however, ODF/OPGL mRNA was undetectable and the expression of OPG/OCIF mRNA was also decreased compared with those in Cbfa1+/+ and Cbfa1+/- embryos. These results suggested that Cbfa1 is somehow involved in osteoclastogenesis through regulation of ODF/OPGL.

Animals↗
PubMed1998

The fucosylation index of alpha-fetoprotein as a possible prognostic indicator for patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to elucidate the usefulness of measuring the fucosylation index (FI) of alpha-fetoprotein (AFP) before the initiation of therapy as a new prognostic indicator for patients with hepatocellular carcinoma (HCC). METHODS: One hundred twelve patients with HCC who underwent transcatheter arterial embolization, chemoembolization, and/or percutaneous ethanol injection were examined in the current study. FI was determined by crossed immunoaffino-electrophoresis in the presence of Lens culinaris agglutinin. RESULTS: When the tentative discriminating value of FI was set at 18%, the mean survival rate for the group whose FI was higher than 18% was significantly lower than that for the group whose FI was equal to or less than 18%, according to the generalized Wilcoxon test (P = 0.0117) and the log rank test (P = 0.0183). The survival rate for HCC patients with AFP concentrations of more than 200 ng/mL was also significantly lower than that for patients with AFP in the range of 21-200 ng/mL, according to the generalized Wilcoxon test (P = 0.0017) and the log rank test (P = 0.0018). When FI was combined with AFP concentration, a highly significant difference was observed between the group with FI >18% and AFP >200 ng/mL and another group with FI < or =18% and AFP < or =200 ng/mL, as determined by the generalized Wilcoxon test (P < 0.0001) and the log rank test (P = 0.0003). An analysis of multiple covariates in the prognostic factors with the Cox proportional hazards model showed that FI was one of the independent prognostic factors. CONCLUSIONS: The current study indicates that measuring FI from sera before the initiation of treatment serves as a new prognostic factor and may improve prognostic estimates and appraisal of therapeutic outcomes for patients with HCC.

Analysis of Variance↗
PubMed1998

The genomic organization of the human corticotropin-releasing factor type-1 receptor.

We determined the genomic organization of human CRF type-1 receptor (hCRF-R1). The gene coding for hCRF-R1 consists of at least 14 exons and spans over 20 kilobases. hCRF-R1's three reported isoforms originate from the same gene by alternative splicing. The first hCRF-R1, which binds to CRF with the highest affinity and transduces the most sensitive cAMP accumulation in response to CRF, is encoded in a total of 13 exons, the only one excluded being exon 6. The second isoform contains an additional 29-amino acid sequence which corresponds to exon 6. Unlike the first isoform, the third lacks a 40-amino acid sequence, corresponding to exon 3. Exon-intron boundaries are the same as that of the consensus sequence. Locations of introns in the coding sequence are similar to human CRF-R1, rat CRF-R1, human CRF-R2alpha and others belonging to the human glucagon receptor family.

Amino Acid Sequence↗
PubMed1998

Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone.

Osteoclast differentiation factor (ODF), a ligand for osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF), induces osteoclast-like cell formation in vitro. To elucidate the role of ODF in the microenvironment of bone, we examined effects of ODF, OPG/OCIF, and anti-ODF polyclonal antibody on bone resorption using a fetal mouse long bone culture system. A genetically engineered soluble-form ODF (sODF) elicited bone resorption in a concentration-dependent manner and OPG/OCIF blocked the bone resorption. Anti-ODF polyclonal antibody, which neutralizes ODF activity, negated bone resorption induced by 1 alpha,25-dihydroxyvitamin D3, parathyroid hormone, or prostaglandin E2. OPG/OCIF also abolished bone-resorbing activity elicited by these bone-resorbing agents. Interleukin 1 alpha-stimulated bone resorption was also significantly suppressed by anti-ODF polyclonal antibody and OPG/OCIF. Thus, we conclude that ODF plays a critical role in bone resorption in the microenvironment of bone.

Animals↗
PubMed1998

Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in human peripheral blood mononuclear cell cultures.

We have reported that osteoclast differentiation factor (ODF) expressed on the plasma membrane of osteoblasts/ stromal cells is a ligand for osteoclastogenesis inhibitory factor (OCIF). A genetically engineered soluble form of ODF (sODF) induced osteoclast-like multinucleated cells (OCLs) in the presence of M-CSF in mouse spleen cell cultures. Osteoblasts/stromal cells were not required in this process. To elucidate the mechanism of human osteoclastogenesis, human peripheral blood mononuclear cells (PBMCs) were cultured for 7 days with sODF and human M-CSF in the presence or absence of dexamethasone. Treatment of human PBMCs with sODF together with M-CSF induced OCLs, which expressed tartrate-resistant acid phosphatase and vitronectin receptors, produced cAMP in response to calcitonin, and formed resorption pits on dentine slices. OCLs were also formed from the adherent cell population of human PBMCs. Dexamethasone was required for human OCL formation in culture of whole PBMCs but not in culture of the adherent cell population. OCL formation was strongly inhibited by OCIF simultaneously added. These results clearly indicate that like in mouse osteoclastogenesis, ODF is a critical factor for human osteoclastogenesis. The present study also indicates that OCIF acts as a naturally occurring decoy receptor for ODF in inhibiting signal transduction in human osteoclast formation.

Animals↗
PubMed1998

The usefulness of determining des-gamma-carboxy prothrombin by sensitive enzyme immunoassay in the early diagnosis of patients with hepatocellular carcinoma.

BACKGROUND: Measurements of serum concentrations of des-gamma-carboxy prothrombin (DCP) are widely used for diagnosing hepatocellular carcinoma (HCC). However, the DCP is not always sensitive enough to detect small HCCs. In the current study, the authors investigated the usefulness of DCP in the early diagnosis of HCC, using a more sensitive enzyme immunoassay than is conventionally employed. METHODS: The authors examined 148 serum samples with DCP concentrations from a conventional assay of less than 100 mAU (arbitrary unit)/mL from 91 patients with HCC and 57 with cirrhosis. DCP concentrations were determined by a more sensitive enzyme immunoassay (ED-036 kit, Eisai Laboratory, Tokyo, Japan) with a minimal detection level of 10 mAU/mL. Ninety-one HCC patients had 43 solitary small HCCs (with a greatest dimension of less than 2 cm). Of these 43 HCCs, 12 were well differentiated. RESULTS: The mean serum concentration of DCP in HCC (48.3 +/- 24.3, mean +/- standard deviation [SD]) was higher than in cirrhosis (20.3 +/- 10.3); this difference was statistically significant. When the tentative cutoff level of 40 mAU/mL (almost corresponding to the mean value + 2SD in patients with cirrhosis) was used as the level of discriminating HCC from cirrhosis, 62% of patients (56 of 91) with HCC had DCP values above this level (sensitivity). However, only three patients with cirrhosis had higher DCP levels. Thus, the specificity of this test was 95% (54 of 57 patients). The total accuracy was 74% (56 + 54/91 + 57). Twenty-three of 43 solitary small HCCs (53%) had DCP values above the cutoff level. Furthermore, 7 of 12 (58%) small, well-differentiated HCCs less than 2 cm in greatest dimension had higher DCP values. CONCLUSIONS: The results of this study indicate that DCP determination by sensitive enzyme immunoassay is useful in the early diagnosis of HCC because a high specificity is maintained.

Adult↗
PubMed1998

Tyrosine phosphorylation of p130Cas is involved in actin organization in osteoclasts.

Integrin-mediated interaction with the extracellular matrix plays a critical role in the function of osteoclasts, the bone-resorbing cells. This study examines the role of p130Cas (Crk-associated substrate (Cas)) in actin organization in osteoclasts. Multinucleated osteoclast-like cells (OCLs) were obtained in a co-culture of murine bone marrow cells and primary osteoblasts. After plating on culture dishes, OCLs formed a ringlike structure consisting of F-actin dots at cell periphery (actin ring). The percentage of OCLs with actin rings and its diameter increased with time and cell spreading. Tyrosine phosphorylation of a protein (p130) increased with actin ring formation. Treatment with cytochalasin D disrupted actin rings and reduced tyrosine phosphorylation of p130. Using specific antibodies, p130 was identified as Cas. By immunocytochemistry, Cas was localized to the peripheral regions of OCLs and its distribution overlapped that of F-actin. In OCLs derived from Src(-/-) mice, in which osteoclast activity is severely compromised, tyrosine phosphorylation of Cas was markedly reduced. Moreover, Cas was diffusely distributed in the cytoplasm and actin ring formation is not observed. These findings suggest that Src-dependent tyrosine phosphorylation of Cas is involved in the adhesion-induced actin organization associated with osteoclast activation.

Actins↗
PubMed1998

Mechanisms of transcription in eosinophils: GATA-1, but not GATA-2, transactivates the promoter of the eosinophil granule major basic protein gene.

Granule major basic protein (MBP) is expressed exclusively in eosinophils, basophils, and placental trophoblasts. To identify the cis-elements and transcription factors involved in regulating MBP expression, we subcloned 3.2 kb of sequence upstream of the exon 9 transcriptional start site (P2 promoter) and serial 5' deletions into the pXP2 luciferase reporter vector. An 80% decrement in promoter activity was obtained when MBP sequences between bp -117 to -67 were deleted. To identify transcription factors that bind to and transactivate through the bp -117 to -67 region, we first compared the upstream genomic sequences of human and murine MBP; a potential GATA binding consensus site was conserved in the 50-bp region between the two genes. To determine which GATA proteins bind this consensus site, we performed electrophoretic mobility shift assays (EMSAs), which showed that both GATA-1 and GATA-2 can bind to this consensus site. To determine the functionality of this site, we tested whether GATA-1 and GATA-2, either individually or in combination, can transactivate the MBP promoter in the Jurkat T cell line. Cotransfection with a GATA-1 expression vector produced 20-fold augmentation of MBP promoter activity, whereas GATA-2 had no activity. In contrast, combined cotransfection of GATA-1 and GATA-2 decreased the ability of GATA-1 to transactivate the MBP promoter by approximately 50%. Our results provide the first evidence for a GATA-1 target gene in eosinophils, a negative regulatory role for GATA-2 in MBP expression, and possibly eosinophil gene transcription in general during myelopoiesis.

Binding Sites↗
PubMed1998

Overexpression of C-terminal Src kinase homologous kinase suppresses activation of Lyn tyrosine kinase required for VLA5-mediated Dami cell spreading.

The Csk homologous kinase (Chk), which is co-expressed with C-terminal Src kinase (Csk) in hematopoietic cells, negatively regulates Src family kinases in vitro with selectivity toward Lyn but not c-Src in platelets. To explore the role of Src family kinases in hematopoietic cell adhesion, we overexpressed Chk in the megakaryocytic cell line Dami and established clones exhibiting a 10-fold increase in the amount of Chk. Overexpression of Chk was found to suppress VLA5 integrin-mediated cell spreading, but not cell attachment, throughout fibronectin (FN) stimulation. Deletion and point mutagenesis analyses of Chk showed that this suppression was dependent upon both the SH3 domain, which is responsible for membrane anchoring, and kinase activity. FN-induced cell spreading accompanied a sustained increase in Lyn activity with coincidental kinetics and the activation of Lyn was also suppressed by overexpression of Chk but not a Chk mutant lacking the SH3 domain. Expression of a truncated Lyn mutant lacking the kinase domain inhibited both cell spreading and Lyn activation upon stimulation with FN. These results suggest that sustained activation of Lyn, which is regulated by membrane-anchored Chk, plays a crucial role in VLA5-mediated cell spreading but not cell attachment to a FN substrate.

Binding Sites↗
PubMed1998

Transgenic expression of Fas in T cells blocks lymphoproliferation but not autoimmune disease in MRL-lpr mice.

Fas is a member of the TNF receptor family. Binding of Fas ligand to Fas induces apoptosis in Fas-bearing cells. Fas is expressed in various cells, including thymocytes, peripheral T cells, and activated B cells. The mouse lpr mutation is a loss of function mutation of Fas. MRL-lpr/lpr mice develop lymphadenopathy and splenomegaly, and produce multiple autoantibodies, which results in autoimmune disease. In this report, we describe the establishment of a line of Fas transgenic MRL-lpr mice in which mouse Fas cDNA was expressed using the T cell-specific murine lck promoter. The transgenic mice expressed functional Fas in thymocytes and peripheral T cells, but not in B cells. The transgenic mice did not accumulate abnormal T cells (Thy-1+ B220+), but still accumulated B cells (Thy-1- B220+); they produced a large quantity of Igs (IgG1 and IgG2a), including anti-DNA Abs, and developed glomerulonephritis. These results suggest that autoreactive or activated B cells must be killed through Fas expressed in the B cells by the Fas ligand expressed in activated T cells.

Animals↗